The long-term goal of our research is to understand the interplay between virus and host, and to use this mediate proteolytic processing of chemokines. mature B cells. In addition, we propose to determine whether HCV directly affects expression of enzymes that We propose to examine the occupancy of chemokine receptors that regulate the trafficking of developing and sites of inflammation or, in the case of B cells, to niches supporting negative selection of autoreactive B cells. chemokine receptor signaling. Such antagonism could block the recruitment or retention of lymphocytes to mononuclear cells may be occupied by proteolytically processed chemokines that act as antagonists of patient B cells often have an unusual CXCR3 phenotype. New data suggest that CXCR3 on peripheral blood dramatically increased circulating levels of chemokines that bind to CXCR3, and at the same time that HCV to test this model are detailed in this application. In addition, we have reported that patients with HCV have a modification of the third model: chronic antigenic stimulation coupled with chronic TLR7 stimulation. Studies data showing overexpression of the RNA pattern recognition receptor TLR7 in HCV patient B cells, we propose stimulation of B cells by HCV envelope proteins, and chronic antigenic stimulation. Based on our preliminary hepatotropic virus induces B lymphocyte dysfunction. The models include direct infection of B cells, polyclonal increased risk of developing non-Hodgkin lymphoma. Several models have been proposed to explain how tissues. MC may be a precursor to B cell non-Hodgkin lymphoma, and HCV patients are known to have a mixed cryoglobulinemia (MC) and symptoms caused by immune complex accumulation in blood vessels and is now the leading indication for liver transplantation. Extrahepatic disease is common and can take the form of between the hepatitis C virus, HCV, and B lymphocytes. HCV causes chronic infection in an estimated 120- knowledge to gain better control over persistent viral infections. In this proposal we examine the interaction 170 million people worldwide. HCV infection leads to cirrhosis, liver failure, and hepatocellular carcinoma, and fl- n a 9(D 0-0 [unreadable]-0v L-0 [unreadable]/1 c-0 N-0 f/1 -=- O-6 0-'.' [unreadable][unreadable]m[unreadable]<W ... [unreadable]m. O[unreadable]> (1) (n. ND( a[unreadable]- .3. '[unreadable]G 0-6 (_o 0 mCD ...